title: PHOX2B mutations in patients with Ondine-Hirschsprung disease and a review of the literature.
abstract: Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is characterized by idiopathic failure of autonomic breathing and is often associated with neurocristopathies such as Hirschsprung disease (HSCR). CCHS is caused by mutations in the paired-like homeobox 2B (PHOX2B) gene, often manifest as polyalanine repeat expansions. Herein, we report the cases of two unrelated Korean patients with Ondine-Hirschsprung disease. The patient's clinical manifestations were apnea and cyanosis requiring immediate endotracheal intubation, recurrent hypoventilation with hypercapnia, hypoxia after ventilator removal, and abdominal distension since birth. Intestinal biopsies were performed and the absence of ganglion cells in the colon was consistent with HSCR. We performed direct sequencing analysis in the PHOX2B and RET genes and fluorescence polymerase chain reaction in order to determine the polyalanine tract expansion in exon 3 of the PHOX2B gene. Expansion mutations were detected in both patients; one had 20/24 repeats and the other had 20/27 repeats. The 20/24 genotype has not been previously described in severe CCHS phenotypes and associated HSCR. We believe that the information in this report will improve our understanding of the phenotypic and genotypic heterogeneities of CCHS and HSCR.
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyeong-dong, Jongno-gu, Seoul, Republic of Korea 110-746.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Gi-Hyuck
authors.initials: GH
authors.lastname: Lee
authors.forename: Myoung-Keun
authors.initials: MK
authors.lastname: Lee
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Hye Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
mesh_terms: D001049:Apnea / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D003490:Cyanosis / Q000235:genetics; D005091:Exons; D005838:Genotype; D006627:Hirschsprung Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007040:Hypoventilation / Q000151:congenital* / Q000235:genetics; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D020182:Sleep Apnea, Central / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret